A user group including nine NIH funded investigators requests $498,113.89 to purchase an integrated TIRF/live cell confocal/fast widefield fluorescence microscope from Intelligent Imaging Innovations (3i) to be housed in the Section of MCB/College of Biological Sciences Imaging Facility. This instrument provides important new live cell imaging capabilities not possible with the two existing "turn key" instruments currently in the facility. This instrument will also free time on the existing point scanning confocal, which will be saturated in the next year. The proposed instrument builds from a base 3i Marianas Real Time Confocal SDC workstation by sharing the laser excitation sources (required for TIRF and multiple-aperture confocal) and sensitive EM-CCD cameras. The system is configured with two separate emission ports that encompass three imaging modalities. One is shared for the TIRF and rapid widefield applications and the other dedicated to the multiple-aperture confocal. Changing between TIRF/widefield and confocal is accomplished using a motorized fiber optic switch which is easily operated by the user. We have demonstrated that this instrument design works well for all three imaging modalities during a weeklong demonstration in our facility by 3i in December 2006. The MCB/CBS Imaging Facility currently serves a very large number of UC-D researchers (64 researchers in 17 departments in fiscal year 2005-2006). The sophisticated and versatile instrument requested here meets the needs of advanced researchers whose research problems and imaging needs have outgrown the capabilities of our existing instrumentation. Three of the major users in this proposal obtained significant new results during our instrument demonstrations that could not be obtained with the existing instrumentation in the Facility. In recognition of the important contribution this instrument would make to the UC-Davis research enterprise, the university administration has pledged $107,691 towards the purchase price. Management of the proposed instrument will be integrated into the existing, successful management scheme (2119 user instrument hours and $96,402 of recharges in fiscal year 2005-2006), which is supervised by a PhD-level scientist and guided by a faculty departmental imaging committee. [unreadable] [unreadable] [unreadable]